【精华】Anesthesiology，A&A 摘要翻译

GoalYou

【第365篇】多巴胺D1受体活化促进异氟烷全身麻醉苏醒 Anesthesiology.2013 Jan;118(1):30-39.

Activation of D1 Dopamine Receptors Induces Emergence from Isoflurane General Anesthesia.

Taylor NE, Chemali JJ, Brown EN, Solt K.

* Clinical Fellow, Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, and Resident, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. ? Research Assistant, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. ? Anesthetist, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; Warren M. Zapol Professor, Department of Anaesthesia, Harvard Medical School; Professor of Computational Neuroscience, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts; Professor of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology. § Assistant Professor, Department of Anaesthesia, Harvard Medical School; Assistant Anesthetist, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; and Research Affiliate, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology.

Abstract

BACKGROUND: A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia.
METHODS: In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose-response study to test for chloro-APB-induced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiologic changes induced by chloro-APB and quinpirole during isoflurane general anesthesia.
RESULTS: Chloro-APB decreased median time to emergence from 330 to 50 s. The median difference in time to emergence between the saline control group (n = 6) and the chloro-APB group (n = 6) was 222 s (95% CI: 77-534 s, Mann-Whitney test). This difference was statistically significant (P = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram δ power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia.
CONCLUSIONS: Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia and produces behavioral and neurophysiologic evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general anesthesia.

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多巴胺D1受体活化促进异氟烷全身麻醉苏醒

背景：最近的一项研究表明哌醋甲酯促进异氟烷全身麻醉苏醒。哌醋甲酯能够抑制多巴胺和去甲肾上腺素的再摄取。本研究旨在验证选择性活化多巴胺受体可促进异氟烷全身麻醉苏醒的假说。

方法：在成年大鼠中，我们检测多巴胺D1受体激动剂（chloro-APB）和D2受体激动剂（quinpirole）对异氟烷全身麻醉苏醒时间的影响。然后，我们对chloro-APB促进持续异氟烷全身麻醉大鼠翻正反射恢复的作用进行剂量相关性研究。D1受体抑制剂（SCH-23390）用于证实chloro-APB通过选择性作用于D1受体发挥促进苏醒的作用。在单独一组动物中，我们对记录到的脑电图进行频谱分析，进而评价在持续异氟烷全身麻醉时chloro-APB和quinpirole对神经生理学影响。

结果：chloro-APB将苏醒中位时间从330s降低到50s。生理盐水组（n=6）和chloro-APB组（n=6）苏醒时间差值的中位数为222s（95% 可信区间: 77-534 s, Mann-Whitney test）。差异具有统计学意义（p=0.0082）。在异氟烷持续麻醉时，chloro-APB剂量依赖性促进翻正反射恢复（n=6）和减少δ 脑电波的活动（n=4）。通过SCH-23390预处理可抑制该作用。在异氟烷持续麻醉时，Quinpirole组未出现翻正反射恢复（n=6）及对脑电图无明显影响（n=4）。

结论：D1受体活化减少异氟烷全身麻醉的苏醒时间，觉醒行为学和神经生理学的证据明其在异氟烷持续全身麻醉时能够促进觉醒。这些发现提示，选择性激活D1受体足以导致异氟烷全身麻醉的苏醒。

GoalYou

【第364篇】硬膜外药物及手术对开放性肾脏手术后膀胱功能的影响：一项临床随机试验研究 Anesthesiology.2013 Jan;118(1):70-7.

Influence of epidural mixture and surgery on bladder function after open renal surgery: a randomized clinical trial.

Wuethrich PY, Metzger T, Mordasini L, Kessler TM, Curatolo M, Burkhard FC.

* Consultant in Anesthesia, § Professor, Department of Anesthesiology and Pain Therapy, ? Resident, ‖ Professor and Vice Chair-woman, Department of Urology, University Hospital Bern, Berne, Switzerland. ? Head of Neuro-Urology, Spinal Cord Injury Center and Research, University of Zürich, Balgrist University Hospital, Zürich, Switzerland.

Abstract

BACKGROUND: In a previous observational study, thoracic epidural analgesia (TEA) after open renal surgery resulted in clinically relevant postvoid residuals (PVRs). This study aimed to investigate the individual contribution of epidurally administrated drugs and surgery in bladder dysfunction.

METHODS: In this single-center, parallel-group, randomized (computer-generated list), double-blind superiority trial, 40 patients undergoing open renal surgery were equally allocated to receive epidural bupivacaine (0.125%) alone or with fentanyl (2 ?g/ml). Patients underwent urodynamic investigations before TEA and during TEA preoperatively and postoperatively. Primary outcome was the difference (Δ) in PVR between before TEA and postoperatively during TEA. Secondary outcomes were changes in detrusor pressure at maximum flow rate, bladder compliance, and ΔPVR between different time points.

RESULTS: Median ΔPVR (ml) from baseline to postoperatively was 180 (range, -85 to 645; P = 0.001) in the bupivacaine group and 235 (range, 0-580; P value less than 0.001) in the bupivacaine/fentanyl group, with no difference between groups (95% confidence interval, -167 to 103; P = 0.634). Detrusor pressure at maximum flow rate (cm H2O) from baseline was more pronounced in the bupivacaine/fentanyl than that in the bupivacaine group preoperatively (-10; range, -64 to -2; P value less than 0.001 vs. -3; range, -35 to 13; P = 0.397) (P = 0.045) and postoperatively (-18; range, -64 to 0; P value less than 0.001 vs. -12; range, -34 to 22; P = 0.006) (P = 0.135). Surgery did not affect PVRs, but a decreased bladder compliance was observed in both groups. No adverse events occurred.

CONCLUSIONS: Thoracic epidurally administrated bupivacaine resulted in clinically relevant PVRs based on impaired detrusor function. The addition of fentanyl enhanced this effect without generating greater PVRs. After surgery, the voiding phase was not further impaired; however, bladder compliance was decreased.

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硬膜外药物及手术对开放性肾脏手术后膀胱功能的影响：一项临床随机试验研究

【摘要】

背景：在之前的一项观察性研究发现，开放性肾脏手术术后采用胸段硬膜外镇痛（TEA）可导致临床相关的尿液残留（PVRs）。该研究旨在研究硬膜外注射药物和手术各自对膀胱功能的影响。

方法：该研究为单中心随机对照双盲试验，40位接受开放性肾脏外科手术的病人随机分为两组。一组接受硬膜外布比卡因（0.125%）注射，另一组接受硬膜外布比卡因和芬太尼（2 ?g/ml）注射。在TEA之前、术前TEA过程中、及术后检测尿动力学变化。研究的主要结果为TEA前和术后TEA中PVR的差别。次要结果包括最高流量时逼尿肌的压力、膀胱顺应性和不同时间点PVR的差别。

结果：布比卡因组，PVR基线值（注：查看全文后“基线值”为TEA前检测值）与术后PVR差值的中位数为180（范围，-85 ~ 645；P = 0.001），布比卡因/芬太尼组为235（范围，0-580；P < 0.001），两组差异无统计学意义（95%可信区间-167~103；P = 0.634）。术前布比卡因/芬太尼组最大流速时逼尿肌的压力值（注：该处指的是“术前TEA后”检测值）与基线值的差值较布比卡因组明显(-10；范围，-64 ~ -2；P< 0.001 vs. -3；范围，-35 ~ 13；P = 0.397) (P = 0.045) ，术后亦如此 (-18；范围， -64 to 0; P value less than 0.001 vs. -12；范围， -34 ~ 22; P = 0.006) (P = 0.135)。手术对PVRs没有影响，但在两组均发现膀胱的顺应性下降。无不良反应发生。

结论：胸段硬膜外注射布比卡因通过影响逼尿肌的功能导致临床相关PVRs。联合注射芬太尼增强对逼尿肌功能的影响，但未发现导致更严重的PVRs。手术对排空期无进一步影响；然而，膀胱的顺应性下降。

GoalYou

【第363篇】吸入含氢气的混合气体可减少新生小鼠暴露于七氟烷后的神经元凋亡及继发的行为异常 Anesthesiology. 2013 Jan;118(1):105-13

Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice.

Yonamine R, Satoh Y, Kodama M, Araki Y, Kazama T.

* Assistant Professor, ? Associate Professor, ? Postgraduate Student, § Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan.

Abstract

BACKGROUND: In animal models, several anesthetics induce widespread increases in neuronal apoptosis in the developing brain with subsequent neurologic deficits. Although the mechanisms are largely unknown, the neurotoxicity may, at least in part, be due to elevated oxidative stress caused by mitochondrial dysfunction. In an investigation of potential therapies that could protect against this type of damage, we studied the effects of molecular hydrogen on anesthetic-induced neurotoxicity in the developing mouse brain.

METHODS: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (< 1.3%) as part of the carrier gas mixture. Apoptosis was evaluated by immunohistochemical staining for cleaved caspase-3 (n = 8-10/group). Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was also performed to examine apoptosis (n = 3-6/group). Oxidative stress was assessed by immunohistochemical staining for 4-hydroxy-2-nonenal (n = 8/group). Long-term memory and social behavior were examined using the fear conditioning test and the sociability test, respectively (n = 18-20/group).

RESULTS: Western blot analysis showed that coadministration of 1.3% hydrogen gas significantly (P < 0.001) reduced the level of neuronal apoptosis to approximately 40% compared with sevoflurane exposure alone. Immunohistochemical analysis showed that hydrogen reduced oxidative stress induced by neonatal sevoflurane exposure. Although neonatal sevoflurane exposure caused impairment in long-term memory and abnormal social behaviors in adulthood, mice coadministered hydrogen gas with sevoflurane did not exhibit these deficits.

CONCLUSIONS: Inhalation of hydrogen gas robustly decreased neuronal apoptosis and subsequent cognitive impairments caused by neonatal exposure to sevoflurane.

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吸入含氢气的混合气体可减少新生小鼠暴露于七氟烷后的神经元凋亡及继发的行为异常

【摘要】

背景：在动物模型中，一些麻醉药物导致大脑发育过程中神经元凋亡增加并继发功能障碍。尽管该机制十分不明确，但认为其神经毒性作用可能一部分与线粒体功能障碍导致的氧化应激损伤有关。为了探索该损伤可能的治疗方法，本实验对氢气在麻醉药物导致小鼠大脑发育过程神经毒性中的作用进行研究。

方法：出生6天的C57BL/6小鼠分别暴露于含有氢气（<1.3%）和不含氢气的七氟烷（3%）中6小时。通过免疫组化检测cleaved caspase-3作为凋亡的指标（n=8-10 每组）。Western blot方法检测多聚腺苷酸二磷酸核糖聚合酶作为凋亡指标（n=3-6 每组）。免疫组化的方法检测4-羟基壬烯醛（4-hydroxy-2-nonenal）作为氧化应激损伤的指标（n=8 每组）。长时记忆和社会活动分别通过恐惧条件化测试（fear conditioning test）和社交能力测试（sociability test）（n=18-20 每组）。

结果：Western blot检测结果发现联合吸入1.3%氢气组与只吸入七氟烷组相比神经元凋亡率下降约40%（P<0.001）。免疫组化研究表明氢气减少新生小鼠七氟烷暴露后的氧化应激反应。尽管，新生小鼠暴露于七氟烷可导致其成年后不可恢复的长时记忆功能和社交能力障碍，但联合吸入氢气组小鼠未表现出这些功能障碍。

结论：吸入氢气可明显减少新生期暴露于七氟烷而导致的神经元凋亡及认知功能障碍。

GoalYou

【第362篇】脂多糖刺激单核细胞通过NFKB1基因启动子-94ins/delATTG影响NFKB1的核转位并增加脓毒症死亡率Anesthesiology. 2013 Jan;118(1):123-133.

The NFKB1 Promoter Polymorphism (-94ins/delATTG) Alters Nuclear Translocation of NF-κB1 in Monocytes after Lipopolysaccharide Stimulation and Is Associated with Increased Mortality in Sepsis.

Adamzik M, Sch?fer S, Frey UH, Becker A, Kreuzer M, Winning S, Frede S, Steinmann J, Fandrey J, Zacharowski K, Siffert W, Peters J, Hartmann M.

* Associate Professor, ? Research Assistant, ? Medical Student, ?? Professor, Klinik für An?sthesiologie und Intensivmedizin, § Associate Professor, ‖ Professor, Institut für Physiologie, # Research Assistant, Institut für Medizinische Mikrobiologie, ?? Professor, Institut für Pharmakogenetik, Universit?t Duisburg-Essen, Universit?tsklinikum Essen, Essen, Germany. ** Professor, Klinik für An?sthesiologie, Intensivmedizin und Schmerztherapie, Klinikum der Goethe Universit?t Frankfurt, Frankfurt, Germany.

Abstract

BACKGROUND: Because the nuclear factor-κB (NF-κB) coupled pathway is believed to amplify inflammation prevailing in sepsis, the authors tested the hypotheses that the insertion-deletion polymorphism (-94ins/delATTG) (1) alters nuclear translocation of nuclear factor-κB and activator protein-1 (NF-κB1) in monocytes after lipopolysaccharide stimulation; (2) affects lipopolysaccharide-induced NF-κB1 messenger RNA expression, tumor necrosis factor α concentrations, and tissue factor activity; and (3) may be associated with increased 30-day mortality in patients with sepsis.

METHODS: Nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation from healthy blood donors was performed with immunofluorescence staining (n = 5 each). Lipopolysaccharide-induced NF-κB1 messenger RNA expression was measured with real-time polymerase chain reaction (PCR; n = 60), tumor necrosis factor α concentrations with a multiplexing system kit (n = 60), and tissue factor activity with thromboelastometry (n = 105). In a prospective study, multivariate proportional hazard analysis tested 30-day mortality in patients with sepsis (n = 143).

METHODS AND RESULTS: The homozygous deletion genotype compared with the homozygous insertion genotype was associated with a nearly twofold increase in nuclear translocation of NF-κB1 (P = 0.001), a threefold difference in NF-κB1 messenger RNA expression (P = 0.001), and a twofold increase in tissue factor expression (P = 0.021). The deletion allele in adults with severe sepsis was tested as an independent prognostic factor for 30-day mortality (hazard ratio, 2.3; 95% CI, 1.13-4.8; P = 0.022). Mortality was 25% for homozygous insertion genotypes but 41% for combined heterozygous deletion/homozygous deletion genotypes (P = 0.034).

CONCLUSION: The deletion allele of the NFκB1 insertion-deletion (-94ins/delATTG) polymorphism is associated with increased 30-day mortality in patients with severe sepsis and increased reaction of the innate immune system.

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脂多糖刺激单核细胞通过NFKB1基因启动子-94ins/delATTG影响NFKB1的核转位并与增加脓毒症死亡率

【摘要】

背景： 由于NF-KB耦合途径可放大脓毒症的炎症反应，因此本研究中我们对下述假设进行验证，基因启动子-94ins/delATTG的插入/缺失突变（1）是否改变单核细胞NF-KB和活化因子-1（NF-KB1）的核转位；（2）是否影响脂多糖诱导NFKB1信使RNA的表达，肿瘤坏死因子的浓度和组织因子的活性；（3）是否与脓毒症患者30天死亡率增加有关。

方法：通过免疫荧光染色方法检测健康献血者的单核细胞被脂多糖刺激后NFKB1的核转位（n=5）。在一项前瞻性研究中，通过多元比例风险分析测试脓毒症患者30天死亡率（n=143）。

结果：纯和基因缺失型与纯和基因嵌入型相比，NFKB1核转位几乎是它的两倍（P = 0.001），NFKB1信使RNA的表达是它的3倍（P = 0.001），组织因子表达是它的2倍（P = 0.021）。严重脓毒血症成年患者该等位基因缺失是30天死亡的独立预测因素 (风险比， 2.3； 95% CI，1.13-4.8；P = 0.022)。纯和基因嵌入型的死亡率为25%，而混合杂合缺失或纯和缺失型的死亡率为41% (P = 0.034)。

结论：NF-κB1基因启动子-94ins/delATTG的缺失与严重脓毒症患者30天死亡率增加有关，增强先天免疫系统反应。

GoalYou

【第361篇】全身应用多奈哌齐通过胆碱能和γ-氨基丁酸机制减轻神经损伤后的高敏反应Anesthesiology. 2013 Jan;118(1):173-80.

Relief of Hypersensitivity after Nerve Injury from Systemic Donepezil Involves Spinal Cholinergic and γ-Aminobutyric Acid Mechanisms.

Kimura M, Hayashida K, Eisenach JC, Saito S, Obata H.

* Graduate Student, § Professor of Anesthesiology, ‖ Associate Professor of Anesthesiology, Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi, Japan. ? Assistant Professor of Anesthesiology, ? FM James, III Professor of Anesthesiology and Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Abstract

BACKGROUND: Evoking spinal release of acetylcholine (ACh) produces antinociception in normal animals and reduces hypersensitivity after nerve injury, and some studies suggest that ACh-mediated analgesia relies on γ-aminobutyric acid (GABA)-ergic signaling in the spinal cord. In this study, the authors tested the spinal mechanisms underlying the antihypersensitivity effects of donepezil, a central nervous system-penetrating cholinesterase inhibitor, in a rat model of neuropathic pain.

METHODS: Male Sprague-Dawley rats were anesthetized, and L5 spinal nerve ligation was performed unilaterally. Withdrawal threshold to a paw pressure test was measured before and after intraperitoneal administration of donepezil, with or without intrathecal antagonists for cholinergic and GABAergic receptors. Microdialysis studies in the ipsilateral dorsal horn of the lumbar spinal cord were also performed to measure extracellular ACh and GABA.

RESULTS: Donepezil increased the withdrawal threshold in spinal nerve ligation rats but not in normal rats. The antihypersensitivity effect of donepezil (1 mg/kg) in spinal nerve ligation rats was reduced by intrathecal pretreatment with atropine (30 μg), a muscarinic receptor antagonist; mecamylamine (100 μg), a nicotinic receptor antagonist; bicuculline (0.03 μg), a γ-aminobutyric acid receptor type A antagonist; and CGP 35348 (30 μg), a γ-aminobutyric acid receptor type B antagonist. ACh and GABA concentrations in the microdialysates from the spinal dorsal horn were increased after intraperitoneal donepezil treatment (1 mg/kg) in both normal and spinal nerve ligation rats.

CONCLUSIONS: Systemic administration of donepezil reduces hypersensitivity after nerve injury by increasing extracellular ACh concentration, which itself induces GABA release in the spinal cord. Activation of this spinal cholinergic-GABAergic interaction represents a promising treatment for neuropathic pain.

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全身应用多奈哌齐通过胆碱能和γ-氨基丁酸机制减轻神经损伤后的高敏反应

【摘要】

背景： 在正常动物中，促进脊髓释放乙酰胆碱可发挥抗伤害作用，减轻脊髓损伤后的高敏反应。一些研究表明乙酰胆碱通过γ-氨基丁酸通路发挥镇痛作用。多奈哌齐是一种可进入中枢神经系统的胆碱酯酶抑制剂，本实验中我们通过大鼠神经病理性疼痛模型，研究多奈哌齐的对抗高敏反应的机制。

方法： 雄性SD大鼠，麻醉后行单侧腰5神经根结扎术。在预先使用或不使用胆碱能和GABA能受体拮抗剂情况下，于腹腔注射多奈哌齐前后，检测大鼠缩足反应的阈值。通过微透析技术检测腰段脊髓同侧脊髓背角细胞外乙酰胆碱和GABA的含量。

结果：多奈哌齐可增加神经根结扎后大鼠的缩足阈值，但对正常大鼠无作用。预先鞘内注射蕈毒碱受体抑制剂阿托品（30 μg)，烟碱受体拮抗剂美卡拉明 (100 μg)，A型γ-氨基丁酸受体拮抗剂荷包牡丹硷(0.03 μg)和B型γ-氨基丁酸受体拮抗剂CGP 35348 (30 μg) 可减轻多奈哌齐（1 mg/kg）在神经根结扎大鼠中的抗高敏反应作用。在正常大鼠和神经根结扎大鼠中，腹腔内注射多奈哌齐后可增加同侧脊髓背角细胞外乙酰胆碱和GABA的含量。

结论： 全身应用多奈哌齐可通过增加细胞外乙酰胆碱含量，进而促进GABA的释放，从而减轻神经损伤后的高敏反应。活化脊髓胆碱能-GABA能受体有希望作为神经病理性疼痛的治疗措施。

GoalYou

【第360篇】泛caspase抑制剂可减轻慢性坐骨神经压迫损伤大鼠的肌细胞凋亡和神经病理性疼痛

Anesth Analg. 2013 Jan;116(1):216-23

A pan-caspase inhibitor reduces myocyte apoptosis and neuropathic pain in rats with chronic constriction injury of the sciatic nerve.

Gradl G, Herlyn P, Finke B, Gierer P, Wree A, Witt M, Mittlmeier T, Vollmar B.

Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, 18057, Rostock, Germany. [email protected].

Abstract

BACKGROUND: Chronic constriction injury is a widely used model for neuropathic pain in rats. It presents with symptoms resembling human neuropathic pain, such as spontaneous pain, hyperalgesia, and allodynia. Recently, myocyte apoptosis was found in neuropathic rats as a possible promoter of pain and motor dysfunction. Our aim in this study was to demonstrate whether muscle cell apoptosis contributes to neuropathic pain in this animal model.

METHODS: To clarify this issue, we examined pain, nutritive perfusion, and inflammation in muscle tissue as well as myocyte apoptosis in rats with neuropathic pain established by chronic constriction injury of the sciatic nerve. Animals received either the pan-caspase inhibitor zVAD (OMe)-fmk (n = 5) or equivalent volumes of vehicle (n = 6). Sham-operated rats served as controls (n = 6).

RESULTS: At day 4 after nerve ligation, there were no signs of perfusion failure or muscle tissue inflammation in all experimental groups. However, animals treated with the vehicle had marked myocyte apoptosis, which was found almost completely blocked in zVA-Dtreated animals. The zVA-Dtreated animals presented with a significant reduction of pain upon heat, cold, and mechanical stimulation comparable with values found in sham controls.

CONCLUSIONS: Myocyte apoptosis possibly contributes to thermal and mechanical allodynia in this experimental model for neuropathic pain. The development of neuropathic pain symptoms did not depend on disturbances in microcirculation or muscle tissue inflammation.
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泛caspase抑制剂可减轻慢性坐骨神经压迫损伤大鼠的肌细胞凋亡和神经病理性疼痛

【摘要】

背景： 慢性压迫损伤是大鼠神经病理性痛常用的动物模型。它可以较好模拟人类的神经病理性疼痛，例如自发性疼痛、痛觉过敏和异常性疼痛。近来，在神经病理性痛大鼠中发现肌细胞凋亡可能促进疼痛和运动功能障碍。本实验旨在验证在该动物模型中肌细胞凋亡是否促进神经病理性疼痛。

方法： 为阐明该问题，我们建立慢性坐骨神经压迫的神经病理性疼痛大鼠模型，检测疼痛、微循环灌注、肌肉组织中的炎症反应以及肌细胞的凋亡情况。实验动物接受泛caspase抑制剂zVAD (OMe)-fmk (n = 5)或者相同剂量的安慰剂(n = 6)。假手术组作为对照组。

结果： 神经结扎后4天，在所有实验组中未出现灌注障碍和肌肉组织炎症的情况。然而，安慰剂处理组出现显著肌细胞凋亡，而在zVAD处理组几乎未出现。与假手术组对比，zVAD处理组对热、冷及机械刺激的疼痛明显减轻。

结论： 在该病理性疼痛动物模型中，肌细胞凋亡可能促进热能和机械痛觉过敏。痛觉过敏的症状与肌肉组织微循环灌注障碍或肌肉炎症反应无关。

GoalYou

【第359篇】蛛网膜下腔和颅内出血患者复极化异常：危险因素及其预后相关性

Anesth Analg. 2013 Jan;116(1):190-7

Repolarization abnormalities in patients with subarachnoid and intracerebral hemorrhage: predisposing factors and association with outcome.

Junttila E, Vaara M, Koskenkari J, Ohtonen P, Karttunen A, Raatikainen P, Ala-Kokko T.

Department of Anesthesiology, Oulu University Hospital, PO Box 21, FIN-90029 OUH, Oulu, Finland. [email protected].

Abstract

BACKGROUND: Electrocardiographic (ECG) abnormalities are frequent in patients with intracranial insult. In this study, we evaluated the factors predisposing to the repolarization abnormalities, i.e., prolonged corrected QT (QTc) interval, ischemic-like ECG changes and morphologic end-repolarization abnormalities, and examined the prognostic value of these abnormalities in patients with subarachnoid and intracerebral hemorrhages requiring intensive care.

METHODS: This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, the level of consciousness, and findings in primary head computed tomography were recorded on admission. The study period was divided into three 2-day sections. In each section, a 12-lead ECG, transthoracic echocardiography, the results of standard blood electrolytes and cardiac troponin I, as well as the rate of vasoactive and sedative drug infusions were recorded. Repolarization abnormalities such as prolongation of the QTc interval (millisecond), ischemic-like ECG changes, and morphologic end-repolarization abnormalities (present/absent) were evaluated and analyzed. The 1-year functional outcome was determined using the Glasgow Outcome Score.

RESULTS: During the 2-year study period, 108 patients were included in the study. Different repolarization abnormalities were frequent in both types of hemorrhage. Prolongation of the QTc interval was predisposed by female gender (β, 24.5; P = 0.010) and the use of propofol (β, 30.5; P = 0.001). The predisposing factor for ischemic-like ECG changes were male gender (odds ratio [OR], 5.9; P = 0.003) and for morphological end-repolarization abnormalities aneurysmatic bleeding (OR, 13.0; P = 0.002). Ischemic-like ECG changes were common, in 87/108 patients during the study period, and were associated with a poorer 1-year functional outcome (OR, 4.7; lower 95% confidence interval, 1.5; P = 0.010).

CONCLUSIONS: Each repolarization abnormality has characteristic predisposing factors. Ischemic-like ECG changes are common and are associated with a poorer 1-year functional outcome.
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蛛网膜下腔和颅内出血患者复极化异常：危险因素及其预后相关性

【摘要】

背景： 颅内病变患者常出现心电图异常。在本研究中，我们评估负极化异常（例如， QT间期延长、缺血样心电图改变和复极化晚期形态异常）相关的危险因素及其作为判断需要监护治疗的蛛网膜下腔及颅内出血患者预后的价值。

方法： 该研究是在大学级别医院ICU内进行的前瞻性观察性临床研究。记录入院时患者临床特点、意识水平及头颅CT检查的主要发现。研究分为3个为期两天的阶段。在每个阶段，记录12导联心电图、经胸壁超声心动图、电解质、心肌肌钙蛋白I及血管活性药物和镇静药物的输注速度。分析和评估负极化异常（例如， QT间期延长、缺血样心电图改变和复极化晚期形态异常）相关的危险因素。通过格拉斯评分评估1年期间患者运动功能恢复情况。

结果： 研究为期2年，共108位患者。在不同类型出血患者中均频繁出现不同程度负极化异常。女性和丙泊酚应用为QT间期延长的危险因素(β, 24.5; P = 0.010)(β, 30.5; P = 0.001) 。 男性是缺血样心电图改变(odds ratio [OR], 5.9; P = 0.003) 和复极化晚期形态异常(OR, 13.0; P = 0.002)的危险因素。缺血样心电图改变发生较为普遍，108位患者中有87位出现，并且与1年期患者功能恢复差有关(OR, 4.7; lower 95% 可信区间, 1.5; P = 0.010)。

结论： 每种不同的负极化障碍有不同的危险因素。缺血样心电图改变发生较为普遍，并且与1年期患者功能恢复差有关。

GoalYou

【第358篇】 地塞米松预防术后恶心呕吐：一项更新的临床随机对照试验Meta分析 Anesth Analg.2013 Jan;116(1):58-74.

Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials.

De Oliveira GS Jr, Castro-Alves LJ, Ahmad S, Kendall MC, McCarthy RJ.

MSCI, Department of Anesthesiology, Northwestern Memorial Hospital, 251 E Huron St, F5-704, Chicago, IL 60611. [email protected].

BACKGROUND: Dexamethasone has an established role in decreasing postoperative nausea and vomiting (PONV); however, the optimal dexamethasone dose for reducing PONV when it is used as a single or combination prophylactic strategy has not been clearly defined. In this study, we evaluated the use of 4 mg to 5 mg and 8 mg to 10 mg IV doses of dexamethasone to prevent PONV when used as a single drug or as part of a combination preventive therapy.

METHODS: A wide search was performed to identify randomized clinical trials that evaluated systemic dexamethasone as a prophylactic drug to reduce postoperative nausea and/or vomiting. The effects of dexamethasone dose were evaluated by pooling studies into 2 groups: 4 mg to 5 mg and 8 mg to 10 mg. The first group represents the suggested dexamethasone dose to prevent PONV by the Society for Ambulatory Anesthesia (SAMBA) guidelines, and the second group represents twice the dose range recommended by the guidelines. The SAMBA guidelines were developed in response to studies, which have been performed to examine different dosages of dexamethasone.

RESULTS: Sixty randomized clinical trials with 6696 subjects were included. The 4-mg to 5-mg dose dexamethasone group experienced reduced 24-hour PONV compared with control, odds ratio (OR, 0.31; 95% confidence interval [CI], 0.23-0.41), and number needed to treat (NNT, 3.7; 95% CI, 3.0-4.7). When used together with a second antiemetic, the 4-mg to 5-mg dexamethasone group also experienced reduced 24-hour PONV compared with control (OR, 0.50; 95% CI, 0.35-0.72; NNT, 6.6; 95% CI, 4.3-12.8). The 8-mg to 10-mg dose dexamethasone group experienced decreased 24-hour PONV compared with control (OR, 0.26; 95% CI, 0.20-0.32; NNT, 3.8; 95% CI, 3.0-4.3). Asymmetric funnel plots were observed in the 8-mg to 10-mg dose analysis, suggesting the possibility of publication bias. When used together with a second antiemetic, the 8-mg to 10-mg dose group also experienced reduced incidence of 24-hour PONV (OR, 0.35; 95% CI, 0.22-0.53; NNT, 6.2; 95% CI, 4.5-10). In studies that provided a direct comparison between groups, there was no clinical advantage of the 8-mg to 10-mg dexamethasone dose compared with the 4-mg to 5-mg dose on the incidence of postoperative nausea and/or vomiting.

CONCLUSIONS: Our results showed that a 4-mg to 5-mg dose of dexamethasone seems to have similar clinical effects in the reduction of PONV as the 8-mg to 10-mg dose when dexamethasone was used as a single drug or as a combination therapy. These findings support the current recommendation of the SAMBA guidelines for PONV, which favors the 4-mg to 5-mg dose regimen of systemic dexamethasone.
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地塞米松预防术后恶心呕吐：一项更新的临床随机对照试验Meta分析

背景： 地塞米松已经被证实能够降低术后恶心呕吐发生率；然而，其作为单独用药或者联合用药用于预防术后恶心呕吐的最佳剂量仍不明确。在本研究中，我们评估4-5mg和8-10mg地塞米松静脉注射作为单独或者联合用药用于预防术后恶心呕吐的作用。

方法：全面检索有关地塞米松全身应用作为预防用药预防术后恶心和/或呕吐的临床随机试验。按照地塞米松的用量，将研究分为两大组：4-5mg组和8-10mg组。第1组是门诊麻醉协会（SAMBA）推荐用于预防PONV的地塞米松剂量，第2组代表该推荐值两倍的剂量。SAMBA指南是根据既往不同剂量地塞米松的研究而制定的。

结果：共纳入6个随机临床试验，6696个患者。4-5mg地塞米松组与对照组相比可降低术后24小时恶心呕吐发生 (OR, 0.31; 95% 可信区间 [CI], 0.23-0.41)及需要治疗的人数(NNT, 3.7; 95% CI, 3.0-4.7)。与其它止吐药物联合使用时，4-5mg地塞米松同样能够降低术后24小时恶心呕吐发生 (OR, 0.50; 95% CI, 0.35-0.72; NNT, 6.6; 95% CI, 4.3-12.8)。8-10mg地塞米松组与对照组相比可降低术后24小时恶心呕吐发生(OR, 0.26; 95% CI, 0.20-0.32; NNT, 3.8; 95% CI, 3.0-4.3)。8-10mg组漏斗图呈不对称型，提示可能存在发表偏倚。与其它止吐药物联合使用时，8-10mg地塞米松同样能够降低术后24小时恶心呕吐发生(OR, 0.35; 95% CI, 0.22-0.53; NNT, 6.2; 95% CI, 4.5-10)。该研究直接比较两组不同剂量地塞米松的作用，结果表明8-10mg组与4-5mg组相比，在降低术后恶心呕吐发生率上没有优势。

结论： 我们的研究结果表明，地塞米松无论是作为单独用药还是与其它止吐药联合应用，4-5mg地塞米松与8-10mg地塞米松具有相同的临床作用。该结论支持SAMBA推荐的地塞米松作为预防术后恶心呕吐的剂量（4-5mg）。

GoalYou

【第357篇 】布比卡因和罗布卡因在心肌细胞蓄积与可逆性线粒体功能异常和心功能减退相 Anesth Analg.2013 Jan;116(1):83-92.

Myocardial accumulation of bupivacaine and ropivacaine is associated with reversible effects on mitochondria and reduced myocardial function.

Hiller N, Mirtschink P, Merkel C, Knels L, Oertel R, Christ T, Deussen A, Koch T, Stehr SN.

DESA, Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany. [email protected].

Abstract

BACKGROUND: Mechanisms of local anesthetic cardiac toxicity are still not completely understood. In this study, we analyzed whether concentrations of local anesthetics found in clinical toxicity affect myocardial mitochondrial structure and oxygen consumption.

METHODS: Guinea pig isolated heart Langendorff preparations were exposed to bupivacaine (3.0 and 7.5 μg/mL) and ropivacaine (3.6 and 9.0 μg/mL) for 10 minutes. Heart rate, systolic blood pressure, the first derivative of left ventricular pressure (+dP/dt), electrocardiogram, and coronary flow were recorded. The local anesthetic tissue concentration was measured either immediately after local anesthetic exposure, or after 20- and 60-minute washout periods. In addition, electron microscopy of myocardial mitochondria was performed using a scoring system for structural damage of mitochondria. Cardiomyocyte cell culture was incubated with bupivacaine, and oxygen consumption ratio, extracellular acidification, and relative amounts of PGC-1α mRNA, a regulator of cellular energy metabolism, were determined.

RESULTS: Bupivacaine and ropivacaine induced reversible PR interval and QRS prolongation, and left ventricular pressure and +dP/dt reduction. Myocardial tissue concentration of local anesthetics was 3-fold the arterial concentration. Mitochondria showed a significant concentration-dependent morphological swelling after local anesthetic application. These changes were reversed by a 20-minute washout period for ropivacaine and by a 60-minute washout for bupivacaine. Bupivacaine reduced mitochondrial oxygen consumption and increased PGC-1α expression in neonatal cardiomyocyte cell cultures, whereas fatty acid metabolism remained unaffected.

CONCLUSIONS: Bupivacaine and ropivacaine accumulate in the myocardium. Reversible local anesthetic-induced mitochondrial swelling occurs at concentrations that induce a negative inotropic effect. Bupivacaine reduces cellular metabolism, whereas this reduction is reversible by fatty acids. Interaction with mitochondria may contribute to the negative inotropic effect of local anesthetics.
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布比卡因和罗布卡因在心肌细胞蓄积与可逆性线粒体功能异常和心功能减退相关

【摘要】

背景： 局麻药心脏毒性的机制仍未完全阐明。在本研究中，我们分析临床上可导致心脏毒性作用的局麻药是否影响心肌细胞线粒体结构和耗氧量。

方法： 用Langendorff法行豚鼠离体心脏灌流，记录布比卡因(3.0 and 7.5 μg/mL)和 罗哌卡因(3.6 and 9.0 μg/mL)作用10分钟后，心率、收缩压、左心室压力(+dP/dt)、心电图和冠脉血流量变化。测定局麻药暴露后即刻、洗脱后20分钟和60分钟组织内局麻药浓度。此外，电子显微镜观察心肌细胞线粒体结构的破坏，并进行评分。体外培养的心肌细胞暴露于布比卡因，检测耗氧量比例、细胞外酸化和细胞能量代谢调节物PGC-1α mRNA的浓度。

结果： 布比卡因和罗哌卡因导致可逆性RP间期和QRS间期延长，左心室压力(+dP/dt)降低。局部组织内局麻药浓度是动脉内的3倍。局麻药导致浓度依赖性线粒体肿胀。这些作用在罗哌卡因洗脱后20分钟，布比卡因洗脱后60分钟可恢复正常。布比卡因导致体外培养心肌细胞线粒体耗氧量降低，PGC-1α mRNA表达增加，对脂肪酸代谢无影响。

结论： 布比卡因和罗哌卡因可在心肌细胞内聚集。导致负性肌力作用浓度的局麻药可导致线粒体肿胀。布比卡因降低细胞代谢，然而，该作用可被脂肪酸逆转。通过对线粒体的作用，局麻药可导致负性肌力作用。

GoalYou

【第356篇 】30mg和45mg利多卡因试验剂量在产科麻醉中预测鞘内注射的前瞻随机临床试验

Anesth Analg.2013 Jan;116(1):125-32.

A Prospective Randomized Trial of Lidocaine 30 mg Versus 45 mg for Epidural Test Dose for Intrathecal Injection in the Obstetric Population.

Pratt S, Hess P, Vasudevan A.

Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. [email protected].

Abstract

BACKGROUND: The epidural test dose, used to identify unintended intrathecal placement, should reliably produce a spinal block without posing a threat to the patient. Most anesthesiologists administer a dose of local anesthetic, commonly lidocaine 45 mg. Pregnant patients are more sensitive to local anesthetics; high and total spinal anesthesia have been reported in the pregnant population with this dose. We hypothesized that lidocaine 30 mg was as effective as lidocaine 45 mg in creating rapid objective evidence of a sensory or motor block.

METHODS: In this prospective, randomized, double-blind trial, patients scheduled for cesarean delivery were assigned to 1 of 4 groups: lidocaine 30 mg in the spinal or epidural space, or lidocaine 45 mg by the same routes. A blinded observer assessed the degree of sensory and motor block. The ability to identify intrathecal injection of each dose was compared. Sensory block above T6 dermatome and hypotension were recorded as side effects.

RESULTS: Intrathecal administration of lidocaine 30 mg produced rapid subjective and objective signs of neuroblockade within 3 minutes (100%, 95% confidence interval CI, 85%-100% for each). Lidocaine 45 mg produced similar results. All patients in both groups described their legs as warm or heavy after 3 minutes and had a motor block by 5 minutes. On the basis of an intrathecal catheter rate of 1:380, the observed negative predictive value for intrathecal placement if the patient described no sensory changes at 3 minutes was 100% (95% CI, 99.95%-100%) for 30 mg and 100% (95% CI, 99.93%-100%) for 45 mg. We did not identify a decrease in the rate of side effects with the lower dose.

CONCLUSIONS: Our results suggest that there is unlikely to be a large difference in the ability of these doses to detect unintentional intrathecal catheter placement. While the negative predictive value for intrathecal injection is very high for both doses, the 95% CI for the sensitivity of either dose is too wide to demonstrate clinical safety to identify all intrathecal catheters. A much larger study is warranted to assess whether there is a lower sensitivity with the 30-mg dose, or a propensity toward high cephalad motor block levels with the 45-mg dose.

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【摘要】

背景： 硬膜外试验剂量旨在确保硬膜外置管未误入鞘内，其能够产生一定程度的脊髓麻醉，但不会对患者造成伤害。绝大多数麻醉医生注射45mg利多卡因进行试验。怀孕的患者较普通患者对局麻药的敏感性高；既往有报道该剂量可导致怀孕患者高位脊髓麻醉和全脊麻。我们假设30mg利多卡因与45mg利多卡因相比同样能够快速导致感觉或运动阻滞。

方法： 该研究为临床随机对照双盲试验，拟行剖宫产的患者随机分配在1-4组：利多卡因30mg蛛网膜下腔或硬膜外注射，或者利多卡因45mg蛛网膜下腔或硬膜外注射。另一观察人员评价感觉和运动阻滞程度。比较每种剂量预测鞘内注射的能力。达到T6水平皮肤感觉阻滞和低血压作为副作用而被记录。

结果： 30mg利多卡因蛛网膜下腔注射可在3min内导致主观和客观的神经阻滞(100%， 95% CI，85%-100%)。45mg利多卡因产生相似结果。不同组别的所有患者描述3min后他们的腿出现发热或发沉现象，5min后出现运动阻滞。根据鞘内置管的比例为1:380，30mg 和45mg 利多卡因注射后，如果患者3min内未出现感觉改变，其鞘内置管的阴性预测值分别为100% (95% CI，99.95%-100%)和100% (95% CI，99.93%-100%)。我们没有发现较低剂量可减少副作用发生率。

结论： 我们的结果表明，我们对比的两种剂量预测误行鞘内置管的作用没有大的区别。而所有剂量鞘内注射的阴性预测值都很高，所有剂量敏感度的95%可信区间太广，很难保证每个鞘内置管的安全性。因此，需要更多的研究来评价是否30mg利多卡因的敏感性较低，或者45mg利多卡因可导致更高平面的运动阻滞。